Construction of Bacteriophage Phi29 DNA Packaging Motor and its Applications in Nanotechnology and Therapy

Abstract

Nanobiotechnology involves the creation, characterization, and modification of organized nanomaterials to serve as building blocks for constructing nanoscale devices in technology and medicine. Living systems contain a wide variety of nanomachines and highly ordered structures of macromolecules. The novelty and ingenious design of the bacterial virus phi29 DNA packaging motor and its parts inspired the synthesis of this motor and its components as biomimetics. This 30-nm nanomotor uses six copies of an ATP-binding pRNA to gear the motor. The structural versatility of pRNA has been utilized to construct dimers, trimers, hexamers, and patterned superstructures via the interaction of two interlocking loops. The approach, based on bottom-up assembly, has also been applied to nanomachine fabrication, pathogen detection and the delivery of drugs, siRNA, ribozymes, and genes to specific cells in vitro and in vivo. Another essential component of the motor is the connector, which contains 12 copies of a protein gp10 to form a 3.6-nm central channel as a path for DNA. This article will review current studies of the structure and function of the phi29 DNA packaging motor, as well as the mechanism of motion, the principle of in vitro construction, and its potential nanotechnological and medical applications.

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Acknowledgments

We thank Dr. Anne Vonderheide, Linda Keller, Dr. Hui Zhang, Feng Xiao, Dr. Farzin Haque, and Mollie Johnson for their assistance in preparing this review. The work done in the author’s laboratory was supported by NIH Grants GM59944, EB03730, and the NIH Nanomedicine Development Center (NDC) of “Phi29 DNA Packaging Motor for Nanomedicine” (PN2 EY018230) through the NIH Roadmap for Medical Research. Peixuan Guo is the cofounder of Kylin Therapeutics, Inc.